PROJECT SUMMARY Following initial smoking cessation, smokers increase their daily caloric intake significantly, an effect observable on day one and lasting for weeks or months. Indeed, within one year, ~50% of abstaining smokers gain >11 lbs. and ~15% gain >22lbs. As such, weight gain is often cited as a primary reason for returning to smoking. While many pharmacologic and behavioral interventions to reduce post-cessation weight gain (PCWG) have been tested, these tend to be ineffective or to have short-lived benefits. Thus, novel therapeutic approaches are urgently needed. This will require identifying new intervention targets based on an improved understanding of the neurobehavioral mechanisms linking smoking cessation and overeating. Toward this end, this project breaks new ground by integrating concepts and tools from the fields of behavioral economics and cognitive neuroscience to accelerate the study of neurobehavioral mechanisms underlying PCWG. The primary aims of this functional magnetic resonance imaging (fMRI) study are: (1) To identify effects of initial smoking cessation on food-related brain activity and behavior; (2) To evaluate the relative contribution of these brain and behavioral processes to post-cessation caloric intake; and (3) To compare baseline differences between smokers and non-smokers. This study will use a validated within-subject cross-over fMRI study design to compare working memory, food cue reactivity, reinforcing value of food, and caloric intake during a 4-day period of ?smoking as usual? vs. a 4-day period of mandatory abstinence (order of conditions counterbalanced). On day 4 of each period, participants will undergo fMRI while completing measures of working memory, food cue reactivity, and food reinforcement. 24-hour daily food recalls will be completed at baseline and during each study period to calculate overall caloric intake and intake of high fat and high sugar foods. The study will include and non-smoking comparison group that undergoes one phase of the study. Support for our predictions would inform testing of novel adjunctive treatments to prevent PCWG, such as computerized neurocognitive exercise training. Further, pre-treatment measures of cognitive may identify smokers who are most likely to need more intensive treatment to manage PCWG.